norpholcodine

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 吗啡烷
• 英文名称: norpholcodine
• 英文别名: 7,8-didehydro-4,5α-epoxy-3-(2-morpholinoethoxy)morphinan-6α-ol；(4R,4aR,7S,7aR,12bS)-9-(2-morpholin-4-ylethoxy)-1,2,3,4,4a,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-7-ol
• 化学式: C₂₂H₂₈N₂O₄
• 分子量: 384.475
• InChiKey: FRTAGKQSFLFNLU-AWTYYCOISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  63.2
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  福尔可定 在 水 作用下， 以 甲醇 、 1,2-二氯乙烷 为溶剂， 反应 4.33h， 生成 norpholcodine 、 alkaline earth salt of/the/ methylsulfuric acid
  参考文献：
  名称：

  Comparative biotransformation of morphine, codeine and pholcodine in rat hepatocytes: identification of a novel metabolite of pholcodine

  摘要：

  1. Pholcodine (3-morpholinoethylmorphine), a semi-synthetic alkaloid, is widely used as an antitussive agent.2. Norpholcodine [7,8-didehydro-4,5alpha-epoxy-3-(2-morpholinoethoxy)morphinan-6alpha-ol] (NP) and pholcodine-N-oxide [1(9a)-dehydro-(4aR,5S,7aR,9cS,12S)-4a, 5,7a,8,9,9a-hexahydro-5-hydroxy-12-methyl-3-morpholinoethoxy-1H-8,9,c-(iminoethano)phenanthro[4,5-bcd] furan-12-oxide] (PNOX) were identified in incubations of pholcodine with freshly isolated rat hepatocytes by liquid chromatography/electrospray-mass spectrometry (LC/ESI-MS).3. Synthesized NP and PNOX were characterized by mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy.4. N-oxidation was the major metabolic pathway for pholcodine, producing a previously unreported metabolite.5. The metabolism of morphine and codeine was also determined using freshly isolated hepatocytes.6. For morphine, 3-glucuronidation was the major metabolic pathway, whilst for codeine it was dealkylation (O- and N-).7. Neither morphine nor its metabolites were metabolites of pholcodine.8. This observation supports the hypothesis that the absence of analgesic activity with pholcodine may be due to less O-dealkylation in vivo.9. Together with the slow biotransformation of pholcodine (k(met) = 0.021 muM min(-1)) in comparison with morphine (k(met) = 0.057 muM min(-1)) and codeine (k(met) = 0.112 muM min(-1)), the results obtained were consistent with its low addiction potential and suggest that its antitussive efficacy is mediated by the parent drug or one of its metabolites other than morphine.

  DOI：

  10.1080/0049825021000017911

文献信息

• Comparative biotransformation of morphine, codeine and pholcodine in rat hepatocytes: identification of a novel metabolite of pholcodine
  作者：M. Jairaj、D. G. Watson、M. H. Grant、A. I. Gray、G. G. Skellern

  DOI：10.1080/0049825021000017911

  日期：2002.1

  1. Pholcodine (3-morpholinoethylmorphine), a semi-synthetic alkaloid, is widely used as an antitussive agent.2. Norpholcodine [7,8-didehydro-4,5alpha-epoxy-3-(2-morpholinoethoxy)morphinan-6alpha-ol] (NP) and pholcodine-N-oxide [1(9a)-dehydro-(4aR,5S,7aR,9cS,12S)-4a, 5,7a,8,9,9a-hexahydro-5-hydroxy-12-methyl-3-morpholinoethoxy-1H-8,9,c-(iminoethano)phenanthro[4,5-bcd] furan-12-oxide] (PNOX) were identified in incubations of pholcodine with freshly isolated rat hepatocytes by liquid chromatography/electrospray-mass spectrometry (LC/ESI-MS).3. Synthesized NP and PNOX were characterized by mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy.4. N-oxidation was the major metabolic pathway for pholcodine, producing a previously unreported metabolite.5. The metabolism of morphine and codeine was also determined using freshly isolated hepatocytes.6. For morphine, 3-glucuronidation was the major metabolic pathway, whilst for codeine it was dealkylation (O- and N-).7. Neither morphine nor its metabolites were metabolites of pholcodine.8. This observation supports the hypothesis that the absence of analgesic activity with pholcodine may be due to less O-dealkylation in vivo.9. Together with the slow biotransformation of pholcodine (k(met) = 0.021 muM min(-1)) in comparison with morphine (k(met) = 0.057 muM min(-1)) and codeine (k(met) = 0.112 muM min(-1)), the results obtained were consistent with its low addiction potential and suggest that its antitussive efficacy is mediated by the parent drug or one of its metabolites other than morphine.